A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis
Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitor...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2011-01-01
|
Series: | Clinical and Developmental Immunology |
Online Access: | http://dx.doi.org/10.1155/2011/305656 |
id |
doaj-2a0203ac93e346899e13bc364a84c272 |
---|---|
record_format |
Article |
spelling |
doaj-2a0203ac93e346899e13bc364a84c2722020-11-24T22:36:30ZengHindawi LimitedClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/305656305656A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid ArthritisMie Oki0Norihiko Watanabe1Takayoshi Owada2Yoshihiro Oya3Kei Ikeda4Yasushi Saito5Ryutaro Matsumura6Yohei Seto7Itsuo Iwamoto8Hiroshi Nakajima9Department of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanDepartment of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanDepartment of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanDepartment of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanDepartment of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanDepartment of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanDepartment of Rheumatology, Allergy, and Clinical Immunology, National Hospital Organization Chiba-East National Hospital, Chiba 260-8712, JapanResearch Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba 289-2511, JapanResearch Center for Allergy and Clinical Immunology, Asahi General Hospital, Chiba 289-2511, JapanDepartment of Allergy and Clinical Immunology, Chiba University Hospital, Chuo-ku, Chiba 260-8670, JapanInhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.http://dx.doi.org/10.1155/2011/305656 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mie Oki Norihiko Watanabe Takayoshi Owada Yoshihiro Oya Kei Ikeda Yasushi Saito Ryutaro Matsumura Yohei Seto Itsuo Iwamoto Hiroshi Nakajima |
spellingShingle |
Mie Oki Norihiko Watanabe Takayoshi Owada Yoshihiro Oya Kei Ikeda Yasushi Saito Ryutaro Matsumura Yohei Seto Itsuo Iwamoto Hiroshi Nakajima A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis Clinical and Developmental Immunology |
author_facet |
Mie Oki Norihiko Watanabe Takayoshi Owada Yoshihiro Oya Kei Ikeda Yasushi Saito Ryutaro Matsumura Yohei Seto Itsuo Iwamoto Hiroshi Nakajima |
author_sort |
Mie Oki |
title |
A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis |
title_short |
A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis |
title_full |
A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis |
title_fullStr |
A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis |
title_full_unstemmed |
A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis |
title_sort |
functional polymorphism in b and t lymphocyte attenuator is associated with susceptibility to rheumatoid arthritis |
publisher |
Hindawi Limited |
series |
Clinical and Developmental Immunology |
issn |
1740-2522 1740-2530 |
publishDate |
2011-01-01 |
description |
Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans. |
url |
http://dx.doi.org/10.1155/2011/305656 |
work_keys_str_mv |
AT mieoki afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT norihikowatanabe afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT takayoshiowada afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT yoshihirooya afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT keiikeda afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT yasushisaito afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT ryutaromatsumura afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT yoheiseto afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT itsuoiwamoto afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT hiroshinakajima afunctionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT mieoki functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT norihikowatanabe functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT takayoshiowada functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT yoshihirooya functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT keiikeda functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT yasushisaito functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT ryutaromatsumura functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT yoheiseto functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT itsuoiwamoto functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis AT hiroshinakajima functionalpolymorphisminbandtlymphocyteattenuatorisassociatedwithsusceptibilitytorheumatoidarthritis |
_version_ |
1725719920415604736 |